Real-world evidence of RET fusion prevalence and testing in patients with metastatic non-small cell lung cancer

Objectives Rearranged during transfection ( RET ) fusion is a driver aberration in non-small cell lung cancer (NSCLC). Approval of RET inhibitors selpercatinib and pralsetinib prompts adequate molecular testing for RET fusions in NSCLC. The aim of this study was to determine changes in the detection of RET fusions and the effect of various testing strategies in stage IV NSCLC patients using real-world data. Materials and methods Patients diagnosed with metastatic non-squamous NSCLC in 2017 and 2019 were selected from Netherlands Cancer Registry (NCR) database and linked to their pathology reports form the Dutch nationwide pathology databank (Palga). Based on these data, RET fusion testing rates, prevalence and laboratory variation were evaluated. Results A total of 3651 patients and 3934 patients were included in 2017 and 2019, respectively. The prevalence of RET fusion in non-squamous NSCLC was 1.3% and 0.7%, in 2017 and 2019, respectively. The overall RET fusion testing rate increased from 22.6% (2017) to 31.8% (2019). Between 2017 and 2019, a shift from FISH (91% to 47%) to RNA-based testing (6% to 46%) for the detection of RET fusions was observed. Conclusion The prevalence calculated from real-world data in the Netherlands with nation-wide coverage was 1.3% in 2017 and 0.7% in 2019. The decrease in detected RET fusions between 2017 and 2019 was associated with decreased use of FISH testing The prevalence of RET fusions in non-squamous NSCLC published in the literature (1–2%) is therefore likely overestimated.